Use of the R-group descriptor for alignment-free QSAR

被引:11
作者
Hirons, L
Holliday, JD
Jelfs, SP
Willett, P
Gedeck, P
机构
[1] Univ Sheffield, Krebs Inst Biomolec Res, Sheffield S10 2TN, S Yorkshire, England
[2] Univ Sheffield, Dept Informat Studies, Sheffield S10 2TN, S Yorkshire, England
[3] Novartis Pharmaceut UK Ltd, Novartis Horsham Res Ctr, Horsham RH12 5AB, W Sussex, England
来源
QSAR & COMBINATORIAL SCIENCE | 2005年 / 24卷 / 05期
关键词
alignment-free; molecular descriptor; R-group descriptor; substituent;
D O I
10.1002/qsar.200510102
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
An R-group descriptor characterises the distribution of some atom-based property, such as elemental type or partial atomic charge, at increasing numbers of bonds distant from the point of substitution on a parent ring system. Application of Partial Least Squares (PLS) to datasets for which bioactivity data and R-group descriptor information are available is shown to provide an effective way of generating QSAR models with a high level of predictive ability. The resulting models are competitive with the models produced by established QSAR approaches, are readily interpretable in structural terms, and are shown to be of value in the optimisation of a lead series.
引用
收藏
页码:611 / 619
页数:9
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